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      • SELECTION OF PEPTIDES THAT BIND TH THE HLA-A2.1 MOLECULE BY MOLECULAR MODELLING

        LIM, JONG-SEOK,KIM, SEUNGMOAK,LEE, HEE GU,LEE, KI-YOUNG,KWON, TAE-JONG,KIM, KILHYOUN 梨花女子大學校 藥學硏究所 1997 藥學硏究論文集 Vol.- No.6

        Cytotoxic T lymphocytes recognize antigenic peptides in association with major histocompatibility complex class I proteins. Although a large set of class I binding peptides has been described, it is not yet easy to search for potentially antigenic peptides without synthesis of a panel of peptides, and subsequent binding assays. In order to predict HLA-A2.1-restricted antigenic epitopes, a computer model of the HLA-A2.1 molecule was established using X-ray crystallography data. In this model nonameric peptide sequences were aligned. In a molecular dynamics (MD) simulation with two sets of peptides known to be presented by HLA-A2.1, it was important to know the anchor amino acid residue preference and the distance between the anchor residues. We show here that the peptides bound to the HLA-A2.1 model structure possess a side chain of C-terminal anchor residue oriented into the binding groove with different distances between the two anchor residues from 15 to 21A. We also synthesized a set of nonamer peptides containing amino acid sequences of Hepatitis B virus protein that were selected on the basis of previously described HLA-A2.1 specific motifs. When results obtained from the MD simulation were compared with functional binding assays using the TAP-deficient cell line T2, it was evident that the MD simulation method improves prediction of the HLA-A2.1 binding epitope sequence. These results suggest that this approach can provide a way to predict peptide epitopes and search for antigenic regions in sequences in a variety of antigens without screening a large number of synthetic peptides.

      • SELECTION OF PEPTIDES THAT BIND TO THE HLA-A2.1 MOLECULE BY MOLECULAR MODELLING

        LIM, JONG-SEOK,KIM, SEUNGMOAK,LEE, HEE GU,LEE, KI-YOUNG,KWON, TAE-JONG,KIM, KILHYOUN 이화여자대학교 생명과학연구소 1996 생명과학연구논문집 Vol.7 No.-

        Cytotoxic T lymphocytes recognize antigenic peptides in association with major his-tocompatibility complex class I proteins. Although a large set of class I binding peptides has been described, it is not yet easy to search for potentially antigenic peptides without synthesis of a panel of peptides, and subsequent binding assays. In order to predict HLA-A2.1-restricted antigenic epitopes, a computer model of the HLA-A2.1 molecule was established using X-ray crystallography data. In this model nonameric peptide sequences were aligned. In a molecular dynamics(MD)simulation with two sets of peptides known to be presented by HLA-A2.1, it was important to know the anchor amino acid residue preference and the distance between the anchor residues. We show here that the peptides bound to the HLA-A2.1 model structure possess a side chain of C-terminal anchor residue oriented into the binding groove with different distances between the two anchor residues from 15 to 21Å. We also synthesized a set of nonamer peptides containing amino acid sequences of Hepatitis B virus protein that were selected on the basis of previously described HLA-A2.1 specific motifs. When results obtained from the MD simulation were compared with functional binding assays using the TAP-deficient cell line T2, it was evident that the MD simulation method improves prediction of the HLA-A2.1 binding epitope sequence. These results suggest that this approach can provide a way to predict peptide epitopes and search for antigenic regions in sequences in a variety of antigens without screening a large number of synthetic peptides.

      • B형 간염 바이러스 단백질에 있어서 HLA-A2에 의해 표현되는 Epitope 펩타이드 들의 분석

        이희구,임종석,김승목,이기영,김희수,김승호,권태종,최인성,정태화,김길현 이화여자대학교 생명과학연구소 1995 생명과학연구논문집 Vol.6 No.-

        The cytotoxic T lymphocyte(CTL) are an important component in host defense mechanism against viral infection. They can recongnize virus-derived peptides presented by the ClassⅠ MHC molecule at the cell surface of the infected cells. On searching for effective CTL epitopes of hepatitis B virus(HBV), we synthesized a distinct set of 9-10 mer peptide containing amino acid sequence of hepatitis B virus surface proteion that are selected on the basis of a computer modeling and the previously described HLA-A2 specific motifs. Binding assay of the synthetic peptides to HLA-A2 molecules using human antigen processing defectantn T2 cells showed what 3 out of 4 synthetic peptides enhaced the expression of HLA-A2 molemule on T2 cell surface. Two anchor positions, namely P2 and P9(or P10) appeared to play a decisive role for binding. Structural chacteristics of the peptides addressed by molecular dynamics simulation was analysed and compared. These peptides also parially triggerd CTL isolatied frmo human peripheral blood mononuclear cells of HBV positive patients, and the response was peptide-specific. These results showed that negatively-charged amino acid residue at P2 hampered binding affinity of the peptides to HLA-A2 molecules, and that binding affinity of the peptides are not always reflected by thier immunogenicity among natural T cell repertoire.

      • B형 간염 바이러스 단백질에 있어서 HLA-A2에 의해 표현되는 Epitope 펩타이드 들의 분석

        이희구,임종석,김승목,이기영,김희수,김승호,권태종,최인성,정태화,김길현 梨花女子大學校 藥學硏究所 1995 藥學硏究論文集 Vol.- No.5

        The cytotoxic T lymphocyte (CTL) are an important component in host defense mechanism against viral infection. They can recongnize virus-derived peptides presented by the Class I MHC molecule at the cell surface of the infected cells. On searching for effective CTL epitopes of hepatitis B virus(HBV), we synthesized a distinct set of 9-10 mer peptide containing amino acid sequence of hepatitis B virus surface protein that are selected on the basis of a computer modeling and the previously described HLA-A2 specific motifs.Binding assay of the synthetic peptides to HLA-A2 molecules using human antigen processing defectant T2 cells showed that 3 out of 4 synthetic peptides enhanced the expression of HLA-A2 molecule on T2 cell surface.Two anchor positions, namely P2 and P9(or P10) appeared to play a decisive role for binding.Structural. characteristics of the peptides addressed by molecular dynamics simulation was analysed and compared.These peptides also partially triggered CTL isolated from human peripheral blood mononuclear cells of HBV positive patients, and the response was peptide-spcific.These results showed that negatively-charged amino acid residue at P2 hampered binding affinity of the peptides to HLA-A2 molecules, and that binding affinity of the peptides are not always reflected by their immunogenicity among natural T cell repertoire.

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